Biomol Ther  
Tenovin-1 Induces Senescence and Decreases Wound-Healing Activity in Cultured Rat Primary Astrocytes
Minji Bang, Onjeon Ryu, Do Gyeong Kim, Darine Froy Mabunga, Kyu Suk Cho, Yujeong Kim, Seol-Heui Han, Kyoung Ja Kwon* and Chan Young Shin*
Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University, Seoul 05029, Republic of Korea
E-mail: chanyshin@kku.ac.kr (Shin CY), kjjasmine@hanmail.net(Kwon KJ)
Tel: +82-2-2030-7834 (Shin CY), +82-2-454-5630 (Kwon KJ)
Fax: +82-2-2049-6192 (Shin CY), +82-2-2030-7899 (Kwon KJ)
Received: June 5, 2018; Revised: June 27, 2018; Accepted: July 3, 2018; Published online: August 10, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence-associated β-galactosidase (SA-β-gal) activity. Tenovin-1-treated astrocytes showed increased SA-β-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-1β, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.
Keywords: Astrocyte, Tenovin-1, Cellular senescence, Wound healing, Senescence-associated secretory phenotype


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